It is well known that low solubility drugs may be formulated as a solid dispersion of a drug in a polymer to improve the bioavailability of poorly soluble drugs. Preferred solid dispersions are formed by spray drying, since this process results in dispersions in which the drug is typically present as non-crystalline drug dispersed homogeneously throughout the polymer. Such solid dispersions are also referred to as molecular dispersions or solid solutions. See, for example, J. Ford, “Current status of solid dispersions,” Pharm. Acta. Helv. 61 (1986) 69-88.
Solvent processing is a preferred manufacturing technique for making solid dispersions. In this process, the drug and polymer are both dissolved in a common solvent. The solvent is then rapidly removed by atomizing the spray solution in the presence of a drying gas. The rapid removal of solvent results in a solid dispersion of the drug in a non-crystalline form (also referred to as amorphous) homogeneously dispersed through the polymer. Such solid dispersions provide high concentrations of dissolved drug in in vitro dissolution tests and good bioavailability.
However, there exists a class of compounds for which it is desired to form solid dispersions in order to improve bioavailability, but which are difficult to prepare as solid dispersions. Such compounds have very low aqueous solubility, as well as very poor solubility in the volatile solvents used to form the spray solution. As a result, such compounds may be impractical to prepare as solid dispersions using the spray drying technique.
Accordingly, it is desired to provide solid dispersions of drugs and polymers, the drug being both poorly aqueous soluble and poorly soluble in volatile organic solvents.